In vitro efficacy of 2,N-bisarylated 2-ethoxyacetamides against Plasmodium falciparum.

Autor: Gutteridge CE; Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA. Electronic address: gutterid@usna.edu., Major JW; Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA., Nin DA; Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA., Curtis SM; Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA., Bhattacharjee AK; Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA., Gerena L; Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA., Nichols DA; Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Feb 01; Vol. 26 (3), pp. 1048-1051. Date of Electronic Publication: 2015 Dec 11.
DOI: 10.1016/j.bmcl.2015.12.032
Abstrakt: Investigation of a series of 2,N-bisarylated 2-ethoxyacetamides resulted in the identification of four inhibitors 5, 20, 24, 29 with single-digit micromolar in vitro efficacy against two drug-resistant Plasmodium falciparum strains. These compounds are analogs of structurally-related 1,3-bisaryl-2-propen-1-ones (chalcones), the latter showing efficacy in vitro but not in a malaria-infected mouse. The 2,N-bisarylated 2-ethoxyacetamides (e.g., 2, 5, 20) were shown to possess significantly greater stability in the presence of metabolizing enzymes than the corresponding 1,3-bisaryl-2-propen-1-ones (e.g., 1, 3, 18).
(Published by Elsevier Ltd.)
Databáze: MEDLINE
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